title: [Identification of a HEK-293 cell line containing stably-transfected H3R gene and screening for novel non-imidazole histamine H3 receptor antagonists].
abstract: OBJECTIVE
  To identify a HEK293 cell line containing stably-transfected H3R gene, and to screen the novel non-imidazole compounds with H3R antagonist activity.
  
  
  METHODS
  The expression of rat H3 receptor in cell line was detected by RT-PCR and Western blot. An elevation of intercellular cAMP concentration induced by forskolin was measured as the index for screening compounds with H3R antagonist activity.
  
  
  RESULTS
  The H3R-transfected HEK-293 cells stably expressed high level of rat H3 receptor mRNA and protein. Forskolin significantly increased intercellular cAMP concentration in the H3R-transfected HEK-293 cells. H3R agonist (R)-α-methylhistamine inhibited the forskolin-induced production of intercellular cAMP. H3R antagonist thioperamide and newly synthesized non-imidazole compounds XHA23 and XHA25 blocked (R)-α- methylhistamine reversal of forskolin-induced cAMP formation in a concentration-dependent manner, and the IC50 values were 3.62 μmol/L, 0.49 μmol/L, 0.14 μmol/L, respectively.
  
  
  CONCLUSIONS
  The H3R-transfected HEK293 cells stably express high level of rat H3 receptor, and can be used for screening compounds with H3R antagonist activity. The non-imidazole compounds XHA23 and XHA25 may have H3R antagonist activity.
authors.affiliation: Department of Pharmacy, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Hu
authors.forename: Haibin
authors.initials: H
authors.lastname: Dai
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D054828:Histamine H3 Antagonists; D006801:Humans; D051381:Rats; D018100:Receptors, Histamine H3 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D054828:Histamine H3 Antagonists; D018100:Receptors, Histamine H3